Pharming enters phase III trials for rhC1INH for hereditary angioedema

Journal of Drugs in Dermatology, Sept-Oct, 2004

Hereditary angioedema (HAE) is a rare but serious condition that manifests as potentially life-threatening angioedema. It is an autosomal dominant disorder manifested by painless, nonpruritic swelling of the skin. Type I HAE is defined by low plasma levels of a normal C1 inhibitor (C1-INH) protein. Type II HAE is characterized by the presence of normal or elevated levels of a dysfunctional C1-INH.

The gene for C1-INH has been mapped to chromosome 11 (11 q12-q13.1). C1-INH is a multifunctional serine protease inhibitor that is normally present in high concentrations in plasma. It is the only known plasma inhibitor of C1r and C1s, the activated proteases of the first component of complement. Uncontrolled activation of the complement system allows for the release of kinin-like mediators, which are thought to result in edema of subcutaneous or submucosal tissues. Pharming Laboratories has developed a recombinant human C1 inhibitor for treatment of this rare condition.

A phase I trial of 12 subjects reported no adverse events, showed no evidence of immune rejection, and demonstrated evidence of systemic availability and activity. Results from the phase II studies showed that all subjects of HAE treated with rhC1INH demonstrated rapid improvement and resolution of angioedema and had favorable evaluation of treatment by both patients and physicians.

In May 2004, Pharming announced the initiation of phase III trials for rhC1INH for the treatment of hereditary angioedema. The double blind, randomized, placebo controlled trial will be conducted at multiple centers across Europe. The study will assess the efficacy and safety of rhC1INH for the treatment of hereditary angioedema. The drug has received Orphan Drug designation from the FDA.